1-Methyl-3-aminopyrazole → HCID 78322291, compound

HRID 2272705Notes

Reaction equation

HRID 2272705 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[N:10]=[C:9]2[C:17]([O:19]CC)=O)=[CH:4][C:3]=1[F:22].[CH3:23][N:24]1[CH:28]=[CH:27][C:26]([NH2:29])=[N:25]1.C[Al](C)C>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[N:10]=[C:9]2[C:17]([NH:29][C:26]2[CH:27]=[CH:28][N:24]([CH3:23])[N:25]=2)=[O:19])=[CH:4][C:3]=1[F:22]

Participants

5

Reactant 3

HCID 1372541-Methyl-3-aminopyrazoleHCID 16682925TrimethylaluminumHCID 86730068HCID 86730068, compound

Product 1

HCID 78322291HCID 78322291, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of ethyl 3-(4-chloro-3-fluorophenyl)-3H-imidazo[4,5-b]pyridine-2-carboxylate (C13) (32 mg, 0.10 mmol) and 1-methyl-1H-pyrazol-3-amine (29 mg, 0.30 mol) in toluene (3 mL) was added trimethylaluminum (2 M solution in toluene, 0.3 mL, 0.6 mmol) at room temperature. The reaction mixture was irradiated in a microwave reactor at 150° C. for 1 hour, whereupon it was partitioned between water (20 mL) and ethyl acetate (50 mL). The organic layer was washed with saturated aqueous sodium chloride solution (20 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Purification via reversed phase HPLC (Column: Agella Venusil ASB-C18, 5 μm; Mobile phase A: 0.225% formic acid in water; Mobile phase B: 0.225% formic acid in acetonitrile; Gradient: 33% to 63% B) afforded the product as a yellow solid. Yield: 2.0 mg, 5.4 μmol, 5%. LCMS m/z 371.1 [M+H]+. 1H NMR (400 MHz, CD3OD) δ 8.47 (br d, J=4.6 Hz, 1H), 8.32 (br d, J=8 Hz, 1H), 7.69 (dd, J=8, 8 Hz, 1H), 7.48-7.56 (m, 3H), 7.35 (br d, J=8 Hz, 1H), 6.52-6.55 (m, 1H), 3.83 (s, 3H).

Workup

  1. customThe reaction mixture was irradiated in a microwave reactor at 150° C. for 1 hour, whereupon it
  2. customwas partitioned between water (20 mL) and ethyl acetate (50 mL)
  3. washThe organic layer was washed with saturated aqueous sodium chloride solution (20 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification via reversed phase HPLC (Column: Agella Venusil ASB-C18, 5 μm; Mobile phase A: 0.225% formic acid in water; Mobile phase B: 0.225% formic acid in acetonitrile; Gradient: 33% to 63% B)

Sources & evidence

ORD record
ord-bc003060dc6845e1a9d852527b03a467
Source dataset
uspto-grants-2015_09
Patent number
US09120788B2

Reaction notes

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